ArticleEpigenetics & chromatin2019
Folate deficiency induced H2A ubiquitination to lead to downregulated expression of genes involved in neural tube defects.
Article in Epigenetics & chromatin, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- A Comprehensive Review of Fortification, Bioavailability, and Health Benefits of Folate.International journal of molecular sciences · 2025Review
- Vitamins and Celiac Disease: Beyond Vitamin D.Metabolites · 2025Review
- Unveiling the Therapeutic Potential of Folate-Dependent One-Carbon Metabolism in Cancer and Neurodegeneration.International journal of molecular sciences · 2024Review
- Identification of potential key ferroptosis- and autophagy-related genes in myelomeningocele through bioinformatics analysis.Heliyon · 2024Article
- Multiplexing of TMT labeling reveals folate-deficient diet-specific proteome changes in NTDs.Frontiers in cell and developmental biology · 2024Article
- Folate deficiency reduced aberrant level of DOT1L-mediated histone H3K79 methylation causes disruptive SHH gene expression involved in neural tube defects.Epigenetics & chromatin · 2023Article
- Intergenerational association of gut microbiota and metabolism with perinatal folate metabolism and neural tube defects.iScience · 2023Article
- Folate and Its Significance in Depressive Disorders and Suicidality: A Comprehensive Narrative Review.Nutrients · 2023Review
- Neural Tube Defects and Folate Deficiency: Is DNA Repair Defective?International journal of molecular sciences · 2023Review
- A quest for genetic causes underlying signaling pathways associated with neural tube defects.Frontiers in pediatrics · 2023Review
- Pathogenesis of neural tube defects: The regulation and disruption of cellular processes underlying neural tube closure.WIREs mechanisms of disease · 2022Review
- Metabolic-epigenetic nexus in regulation of stem cell fate.World journal of stem cells · 2022Review
- Overview of Neural Tube Defects: Gene-Environment Interactions, Preventative Approaches and Future Perspectives.Biomedicines · 2022Review
- Folate-deficiency induced acyl-CoA synthetase short-chain family member 2 increases lysine crotonylome involved in neural tube defects.Frontiers in molecular neuroscience · 2022Article
- Abnormal transcriptome-wide DNA demethylation induced by folate deficiency causes neural tube defects.Frontiers in genetics · 2022Article
- Efficacy of microsurgery for congenital neural tube defects in newborns.American journal of translational research · 2022Article
- Ethionine-mediated reduction of S-adenosylmethionine is responsible for the neural tube defects in the developing mouse embryo-mediated m6A modification and is involved in neural tube defects via modulating Wnt/β-catenin signaling pathway.Epigenetics & chromatin · 2021Article
- Micronutrient imbalance and common phenotypes in neural tube defects.Genesis (New York, N.Y. : 2000) · 2021Review
- Mapping of folic acid in the children brainstem.Anatomy & cell biology · 2021Article
- Aberrant Gcm1 expression mediates Wnt/β-catenin pathway activation in folate deficiency involved in neural tube defects.Cell death & disease · 2021Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundNeural tube defects (NTDs) are common congenital malformations resulting in failure of the neural tube closure during early embryonic development. Although it is known that maternal folate deficiency increases the risk of NTDs, the mechanism remains elusive.
resultsHerein, we report that histone H2A monoubiquitination (H2AK119ub1) plays a role in neural tube closure. We found that the folate antagonist methotrexate induced H2AK119ub1 in mouse embryonic stem cells. We demonstrated that an increase in H2AK119ub1 downregulated expression of the neural tube closure-related genes Cdx2, Nes, Pax6, and Gata4 in mouse embryonic stem cells under folate deficiency conditions. We also determined that the E3 ligase Mdm2 was responsible for the methotrexate-induced increase in H2AK119ub1 and downregulation of neural tube closure-related genes. Surprisingly, we found that Mdm2 is required for MTX-induced H2A ubiquitination and is recruited to the sites of DSB, which is dependent on DNA damage signaling kinase ATM. Furthermore, folic acid supplementation restored H2AK119ub1 binding to neural tube closure-related genes. Downregulation of these genes was also observed in both brain tissue of mouse and human NTD cases, and high levels of H2AK119ub1 were found in the corresponding NTDs samples with their maternal serum folate under low levels. Pearson correlation analysis showed a significant negative correlation between expression of the neural precursor genes and H2AK119ub1.
conclusionOur results indicate that folate deficiency contributes to the onset of NTDs by altering H2AK119ub1 and subsequently affecting expression of neural tube closure-related genes. This may be a potential risk factor for NTDs in response to folate deficiency.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.